The long-term objectives are to clarify electrical and chemical mechanisms of signaling in the nervous system through rigorous and quantitative thinking about ionic channels, receptors, G proteins, second messengers, and transmitter turnover. The primary methods will be whole-cell patch-clamp recording with many biochemical interventions using isolated single cells. Signaling mechanisms that modulate currents in voltage-gated Ca channels and other channels will be characterized in mammalian superior cervical ganglion cells and medium spiny neurons. This will include actions of monoamine transmitters, GABA, peptides, and cannabinoids. Such studies will inventory and describe a network of interacting intracellular signals coupling between receptors and ionic channels that they control in neurons. They will give more quantitative information on the speed and intensity of pathways mediated by different second messenger systems, and will eventually allow theoretical reconstruction of neuronal responses. The radius of action and the rate of uptake of monoamine transmitters will be determined by voltammetry and anatomical studies to gauge the specificity of central signaling pathways. The biophysical properties of various understudied voltage-gated and ligand-gated channels will be determined. The results will bear on the basic neuroscience of signaling. The modulatory actions to be studied are disturbed in schizophrenia, Parkinsonism, and mood and emotional disorders.